Project Summary/Abstract Rationale: Anterior cruciate ligament reconstruction (ACLR) is complicated by high failure rates in young active individuals. Failure of ACLR is associated with limited activity, reduced quality of life, increased socioeconomic costs and higher rates of osteoarthritis (OA). A lateral extra-articular tenodesis (LET) may provide greater stability to the ACLR; but, its effect on failure rate is unclear and surgery-induced lateral compartment OA is a concern. A meta-analysis suggests that bone-patellar-tendon-bone (BPTB) grafts provide better stability compared to a hamstring tendon (HT) grafts, albeit with greater donor site morbidity. Recently, the quadriceps tendon (QT) has become a popular graft choice claiming stability equivocal to BPTB but without donor site morbidity. By evaluating whether one graft is superior at reducing failure rates and minimizing donor site morbidity and by determining whether the addition of an LET contributes to reduced failure, this study (STABILITY 2) addresses NIAMS? mission to contribute to knowledge related to the treatment and prevention of arthritis and NIH?s mission to enhance health and reduce disability. Specific Aims: 1. To determine if graft type (QT, BPTB or HT) with or without a LET affects the rate of graft failure 2 years after ACLR. 2. To determine if graft type (QT, BPTB or HT) with or without a LET affects patient-reported symptoms, function & QOL, performance-based measures of function and return-to-sports 2 years after ACLR. 3. To determine if graft type (QT, BPTB or HT) with or without LET affects rates of intervention-related donor site morbidity, complications and adverse outcomes 2 years after ACLR. 4. To determine if the addition of a particular graft type (QT, BPTB or HT) with or without a LET is a more cost-effective approach to ACLR. Methods: This study will include 21 sites across the USA, Canada, and Europe and will randomly assign 1200 patients to either QT (+/- LET) or BPTB (+/- LET). Randomization will be stratified by surgeon, sex and the status of the meniscus. Patients will follow a standardized rehabilitation protocol. Outcomes will be assessed over two years postoperative by a blinded evaluator and include failure status, functional performance, patient-reported function, quality of life and return-to-sport; presence of donor site morbidity, lateral joint space narrowing; and costs associated with failure. Data from a previously performed HT+/- LET RCT (STABILITY 1) will be combined with STABILITY 2 data. Analyses will follow intention-to-treat and primarily consist of mixed effects modeling.